Washington University Research Articles

Introduction to the Third Generation Simulation Dataset: Data Collection and Trajectory Extraction

This study aims to provide accurate trajectory datasets capable of characterizing human–automated vehicle interactions under a diverse set of scenarios in diverse highway environments. Distinct methods were utilized to collect data from Level 1, Level 2, and Level 3 automated vehicles: (1) fixed location aerial videography (a helicopter hovers over a segment of interest); (2) moving aerial videography (a helicopter follows the automated vehicles as they move in a much longer segment than in the first method); and (3) infrastructure-based videography (multiple overlapping cameras located on overpasses creating a comprehensive image of the study area). Utilizing the fixed location aerial videography approach, trajectories were extracted on I-90/I-94 in Chicago, IL. The moving aerial videography approach was adopted to extract four datasets on I-90/I-94 and I-294 in Chicago, IL. Finally, two datasets were collected on I-395 and George Washington University Campus in Washington, D.C., using the infrastructure-based videography approach. Extracting multiple complete and accurate vehicle trajectories raises a set of methodological and practical challenges that vary across the three data measurement approaches. The methodological details to extract these trajectories are presented in this paper along with the lessons learned with respect to data collection setup, instrumentation, and experimental design efforts.

Self, Physician, and Specialty: A Qualitative Exploration of Medical Students' Specialty Identity Formation During Undergraduate Medical Training.

A physician's specialty is an integral part of their professional identity formation (PIF), not only determining the role they play in patient care but also shaping group interactions in the workplace. Prior work on PIF in medical students has focused on the development of a physician identity. However, little is known about how medical students might begin to develop divergent specialty-specific identities during medical school. Consequently, the authors aimed to explore how the process of specialty selection shapes PIF during undergraduate medical training and to develop a construct of specialty identity formation (SIF) as an important aspect of PIF. The authors used a constructivist grounded theory approach to explore SIF in senior medical students at the University of Washington between August 2022 and January 2023. The author team consisted of 6 attending physicians. Two investigators conducted hour-long, semistructured interviews, which were audio recorded, transcribed, and deidentified. After analysis, member checking was completed with 2 participants. The authors interviewed 14 students and categorized the data into 3 phases: nascent understanding, experiential grounding, and projecting forward. Participants reflected on considering their personal values, while simultaneously exploring the values and defining features of various specialty groups. Early impressions were formed based on ideas influenced by peers and mentors and later integrated with experiences on clinical rotations. Finally, participants noted engaging in a process projecting forward as they attempted to envision their potential futures as both physicians and members of a specialty group. As students explore their specialty identity, they use self-anchoring and self-stereotyping to integrate components of their evolving specialty identity into their professional identity. However, uncertainty regarding their fit with a specialty persists for many. Many sociocultural aspects of the learning environment affect SIF, including threats to psychological and identity safety.

Genetic and multi-omic resources for Alzheimer disease and related dementia from the Knight Alzheimer Disease Research Center

The Knight-Alzheimer Disease Research Center (Knight-ADRC) at Washington University in St. Louis has pioneered and led worldwide seminal studies that have expanded our clinical, social, pathological, and molecular understanding of Alzheimer Disease. Over more than 40 years, research volunteers have been recruited to participate in cognitive, neuropsychologic, imaging, fluid biomarkers, genomic and multi-omic studies. Tissue and longitudinal data collected to foster, facilitate, and support research on dementia and aging. The Genetics and high throughput -omics core (GHTO) have collected of more than 26,000 biological samples from 6,625 Knight-ADRC participants. Samples available include longitudinal DNA, RNA, non-fasted plasma, cerebrospinal fluid pellets, and peripheral blood mononuclear cells. The GHTO has performed deep molecular profiling (genomic, transcriptomic, epigenomic, proteomic, and metabolomic) from large number of brain (n = 2,117), CSF (n = 2,012) and blood/plasma (n = 8,265) samples with the goal of identifying novel risk and protective variants, identify novel molecular biomarkers and causal and druggable targets. Overall, the resources available at GHTO support the increase of our understanding of Alzheimer Disease.

Pretransplant desensitization of donor-specific anti-HLA antibodies with plasmapheresis and immunoglobulin produces equivalent outcomes to patients with no donor specific antibodies in haploidentical hematopoietic cell transplant

Haploidentical hematopoietic cell transplants (haplo-HCT) with donor-specific anti-HLA antibodies (DSAs) are associated with high rates of primary graft failure and poor overall survival (OS). Limited data exists regarding the effect of desensitization. Our institution began routine desensitization for patients with DSAs in 2014. Adult patients undergoing haplo-HCT at Washington University from 2009–2021 were identified and divided into three cohorts: no DSA, untreated DSA (2009–2014) or treated DSA (2014–2021). Desensitization therapy using plasmapheresis and IVIg was performed. Retrospectively, 304 patients were identified. 14 of 30 patients with DSAs underwent desensitization. By day +2, 57% of patients cleared all DSAs. After multivariable analysis, OS was similar between treated DSA and no DSA (HR: 0.69, p = 0.37). Untreated DSA had significantly lower OS compared to no DSA group (HR 1.80, p = 0.046). Desensitization with a backbone of plasmapheresis and IVIg before haplo-HCT may produce similar outcomes to patients without DSAs.

Extracellular electron transfer explained

Extracellular electron transfer explained Arpita Bose, PhD from Washington University in St. Louis, guides us through host-associated impacts and biotechnological applications of extracellular electron transfer in electrochemically active bacteria. Electron flow and oxidative and reductive reactions, referred to as “redox reactions,” collectively impact the outcomes of biochemical pathways essential for cell growth, energy conservation, and stress response throughout various organisms. An example of these organisms is electrochemically active bacteria (EAB), which can link internal redox reactions with external electron acceptors or donors via a process known as extracellular electron transfer (EET).

Predicting cochlear implant performance: Impact of demographic, audiologic, surgical factors, and cochlear health

Predicting cochlear implant performance: Impact of demographic, audiologic, surgical factors, and cochlear health Amit Walia, Matt Shew and Craig A. Buchman from Washington University School of Medicine, explain the challenges of understanding variables or factors informing CI performance and how this can be addressed. Cochlear implants (CIs) are highly effective for restoring hearing in individuals with moderate-to-profound hearing loss who do not gain sufficient benefit from hearing aids. Despite being one of modern medicine’s most successful advancements, there is wide inter-individual variability in speech perception outcomes (Figure 1). The drivers of this variability are not well understood, making it difficult to set realistic expectations for patients before surgery and to evaluate potential interventions that may enhance performance post-operatively. Accurate prediction of speech perception performance after surgery could significantly impact how we assess candidates, plan postoperative aural rehabilitation, choose surgical techniques, design and fit electrodes, and segment the patient population in future CI clinical trials.

A Comprehensive Head-to-Head Comparison of Key Plasma Phosphorylated Tau 217 Biomarker Tests.

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarkers for reliable detection of Alzheimer's disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET, and cognition as outcomes, and benchmarked them against cerebrospinal fluid (CSF) biomarker tests. Samples from 998 individuals (mean[range] age 68.5[20.0-92.5], 53% female) from the Swedish BioFINDER-2 cohort were analyzed. Plasma p-tau217 was measured with mass spectrometry (MS) assays (the ratio between phosphorylated and non-phosphorylated [%p-tau217WashU]and ptau217WashU) as well as with immunoassays (p-tau217Lilly, p-tau217Janssen, p-tau217ALZpath). CSF biomarkers included p-tau217Lilly, and the FDA-approved p-tau181/Aβ42Elecsys and p-tau181Elecsys. All plasma p-tau217 tests exhibited high ability to detect abnormal Aβ-PET (AUC range: 0.91-0.96) and tau-PET (AUC range: 0.94-0.97). Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (P diff<0.007). For detecting Aβ-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 91% (immunoassays: 84-87%), and a specificity of 94% (immunoassays: 85-89%). Among immunoassays, p-tau217Lilly and plasma p-tau217ALZpath had higher AUCs than plasma p-tau217Janssen for Aβ-PET status (P diff<0.006), and p-tau217Lilly outperformed plasma p-tau217ALZpath for tau-PET status (P diff=0.025). Plasma %p-tau217WashU exhibited higher associations with all PET load outcomes compared to immunoassays; baseline Aβ-PET load (R2: 0.72; immunoassays: 0.47-0.58; Pdiff<0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38-0.45; Pdiff<0.001), longitudinal Aβ-PET load (R2: 0.53; immunoassays: 0.31-0.38; Pdiff<0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35-0.43; Pdiff<0.014). Among immunoassays, plasma p-tau217Lilly was more strongly associated with Aβ-PET load than plasma p-tau217Janssen (P diff<0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all P diff<0.010). Plasma %p-tau217 also correlated more strongly with baseline cognition (Mini-Mental State Examination[MMSE]) than all immunoassays (R2 %p-tau217WashU: 0.33; immunoassays: 0.27-0.30; P diff<0.024). The main results were replicated in an external cohort from Washington University in St Louis (n =219). Finally, p-tau217Nulisa showed similar performance to other immunoassays in subsets of both cohorts. In summary, both MS- and immunoassay-based p-tau217 tests generally perform well in identifying Aβ-PET, tau-PET, and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for AD pathology, while some immunoassays might be better suited as triage tests where positive results are confirmed with a second test.

Towards Sustainable Architecture: Energy Storing Bricks and Photovoltaic Systems for Self-Sufficient Residential Housing

This paper addresses the urgent global challenge of climate change by proposing a novel approach to residential architecture that combines passive design with active energy systems. Current studies show that buildings contribute 30% of the global energy consumption and is expected to increase with worldwide rising energy demands including in Indonesia. Studies have shown the abundance of solar exposure in Indonesia. This calls for the maximisation of photovoltaic system an electricity generation system that produces the least amount of CO2. The existing public preference of bricks as residential building materials for its structural integrity and passive design qualities highlights the potential of implementing energy storing bricks technology findings from Washington University. This paper presents a concept that combines photovoltaic (PV) systems with energy-storing bricks to create a self-sufficient home that can produce and store its own electricity. Our goal is to optimize both passive and active design approaches in order to maintain or enhance the standard of living that exists today while simultaneously move toward a sustainable future at the same time. Further empirical research is required to confirm the viability and efficiency of this innovative architectural approach.

Transforming Lung Cancer Care: Advancements in Screening, Treatment, and Survivorship

Matthew Triplette, Fred Hutchinson Cancer Center and University of Washington, Seattle, USA, delivered an insightful talk at the American Thoracic Society (ATS) International Conference 2024 on how landmark studies in lung cancer screening can affect recommendations and standards of care for pulmonary medicine specialists. Triplette highlighted that lung cancer remains the leading cause of cancer-related deaths, with 85% of all lung cancer cases related to tobacco smoke worldwide.

Flipping the script: A multiyear assessment and comparison of flipped classroom versus traditional didactic teaching at two academic institutions

Rationale and objectivesHistorically radiology resident education has taken the form of workstation and didactic teaching. Due to increasing clinical demand and administrative burden for academic radiologists, the need for more efficient and effective teaching has increased. Flipped classroom teaching, where trainees independently learn material prior to interactive teaching sessions with faculty, is a possible alternative. While the use of flipped teaching in radiology has been studied in the medical student setting, its use in the radiology residency setting has been less published. Materials and methodsAt two academic institutions (University of Washington and Northwestern), exam scores from five PGY-2 Core rotations were collected. Flipped teaching was used for one rotation at the University of Washington (FR). The influence of teaching method, rotation, and institution on exam score was examined. Resident surveys were also collected to understand perceptions of flipped classroom teaching. ResultsAt the University of Washington, the mean exam score for the flipped rotation was significantly higher than the majority of other rotations utilizing traditional teaching (p<0.05). Between the University of Washington and Northwestern, there was no difference in exam scores when comparing comparable rotations. Among residents at the University of Washington, the flipped teaching rotation was perceived as more educationally valuable than traditional teaching rotations. ConclusionFlipped classroom teaching is at least as effective as the traditional teaching model and associated with better performance on standardized exams at one institution. Among residents, flipped learning is also associated with higher perceived educational value.

Qualitative Evaluation of an Antimicrobial Stewardship Tele-Mentoring Program in US Rural &amp; Critical Access Hospitals

Background: The University of Washington (UW) Center for Stewardship in Medicine (CSiM) supports a tele-antimicrobial stewardship (AMS) program (TASP) using the ECHO approach (Extension for Community Healthcare Outcomes) in small, rural, and Critical Access Hospitals (primarily in the western U.S.) with education, mentoring, organizational capacity building, and a community of peers. To evaluate the continuing education (CE) component of UW-TASP ECHO, CSiM surveyed individuals receiving CE credits as part of the program. This survey was designed to track individuals’ satisfaction with the program and to assess the impact of UW-TASP ECHO on AMS in participating facilities. Methods: The CE participants’ survey was completed annually by individuals participating in UW TASP ECHO using online survey software. The survey included closed-ended and open-ended questions. Responses to open-ended questions were entered into Atlas.ti qualitative analysis software and coded iteratively according to themes that emerged. When a new code emerged partway through the coding process, earlier surveys were re-coded for the new code. Final codes were grouped into themes and sub-themes and quotes from each theme identified were summarized and attached to the theme and reported. Results: Data from three administrations of this survey were available: 2018-2019 (n=66); 2020-2021 (n=27); and 2021-2022 (n=30). These surveys were completed by a total of 95 individuals from 53 hospitals. Seven of these individuals completed a survey in each year, 14 completed a survey in two years, and 74 completed only one survey. Themes identified were COVID-19 support (including procedures and policies, being kept up-to-date, research summaries, and peer support), the antibiotic pocket guide developed by UW, strength in community, staff education, role of CSiM in developing/strengthening the AMS program at the facility, change in use of antibiotics, UW imprimatur, learning/growing as a healthcare provider, and importance for small, rural hospitals (see examples in Table 1). Conclusions: This qualitative analysis provides evidence from surveys of individuals participating in CE that UW TASP ECHO has had a meaningful impact in such domains as building a strong community among small, rural and critical access hospitals, educating staff, changing antibiotic use and providing peer support, among others.

Evaluating the Accelerated BSN Program at the University of Washington and Its Potential for Implementation in China.

Nurses are the largest group in the health care system. The current care shortage remains a global challenge in the healthcare system.The accelerated second-degree nursing (ABSN) program was first proposed by the University of St.Louis in 1971 and then vigorously developed in the United States. Its purpose is to train more nursing talents to solve the medical needs of the poor in the United States. In the past few decades, this project has been carried out by many countries around the world to solve their domestic nursing problems.As a strategy to address severe care shortages, ABSN is continuing to increase rapidly.China as the world's second most populous country, coupled with aging year by year, the demand for nursing talents, and the ABSN project just gave China effective inspiration.Therefore, this article introduces the basic design of the bachelor's degree in nursing at the University of Washington, summarizes the characteristics of the training model, and draws on experience from the basic situation, training objectives, courses and evaluation methods. It is urgent to provide guidance and reference for the acceleration of nursing education in China.

A Bicultural Community-Academic Partnership to Improve the Latina/o Physician Workforce in Washington State (2019-2021).

From July 2019 through April 2021, the Latino Center for Health, a bicultural population health research center at the University of Washington, partnered with community stakeholders to generate evidence to inform elected officials about the need to increase the diversity of the state's physician workforce and ultimately improve Latina/o health in Washington state. Legislative efforts resulted in legislation creating goals for the state's medical schools to admit students representative of the state's population diversity and the creation of a new residency pathway for international medical graduates. (Am J Public Health. 2024;114(S6):S467-S471. https://doi.org/10.2105/AJPH.2024.307627) [Formula: see text].

Leveraging GPT-4 for identifying cancer phenotypes in electronic health records: a performance comparison between GPT-4, GPT-3.5-turbo, Flan-T5, Llama-3-8B, and spaCy's rule-based and machine learning-based methods.

Accurately identifying clinical phenotypes from Electronic Health Records (EHRs) provides additional insights into patients' health, especially when such information is unavailable in structured data. This study evaluates the application of OpenAI's Generative Pre-trained Transformer (GPT)-4 model to identify clinical phenotypes from EHR text in non-small cell lung cancer (NSCLC) patients. The goal was to identify disease stages, treatments and progression utilizing GPT-4, and compare its performance against GPT-3.5-turbo, Flan-T5-xl, Flan-T5-xxl, Llama-3-8B, and 2 rule-based and machine learning-based methods, namely, scispaCy and medspaCy. Phenotypes such as initial cancer stage, initial treatment, evidence of cancer recurrence, and affected organs during recurrence were identified from 13646 clinical notes for 63 NSCLC patients from Washington University in St. Louis, Missouri. The performance of the GPT-4 model is evaluated against GPT-3.5-turbo, Flan-T5-xxl, Flan-T5-xl, Llama-3-8B, medspaCy, and scispaCy by comparing precision, recall, and micro-F1 scores. GPT-4 achieved higher F1 score, precision, and recall compared to Flan-T5-xl, Flan-T5-xxl, Llama-3-8B, medspaCy, and scispaCy's models. GPT-3.5-turbo performed similarly to that of GPT-4. GPT, Flan-T5, and Llama models were not constrained by explicit rule requirements for contextual pattern recognition. spaCy models relied on predefined patterns, leading to their suboptimal performance. GPT-4 improves clinical phenotype identification due to its robust pre-training and remarkable pattern recognition capability on the embedded tokens. It demonstrates data-driven effectiveness even with limited context in the input. While rule-based models remain useful for some tasks, GPT models offer improved contextual understanding of the text, and robust clinical phenotype extraction.

Ask me anything: Daniel Hook

Daniel Hook is chief executive of Digital Science, a co-founder of the research-information management provider Symplectic, and of the Research on Research Institute. A theoretical physicist by training, he still does research in his spare time, with visiting positions at Imperial College London and Washington University in St Louis.

Uncertainty and Communication Preferences Among Patients Undergoing Lung Transplant Evaluation: A Mixed-Methods Study.

Higher uncertainty is associated with poorer quality of life and may be impacted by clinician communication about the future. We determined how patients undergoing lung transplant evaluation experience uncertainty and communication about the future from clinicians. We performed a convergent parallel mixed-methods study using a cross-sectional survey and semistructured interviews. Patients undergoing lung transplant evaluation at the University of Colorado and the University of Washington answered questions about future communication and completed the Mishel Uncertainty in Illness Scale-Adult (MUIS-A; range 33-165, higher scores indicate more uncertainty). Interviews were analyzed using content analysis. Integration of survey and interview results occurred during data interpretation. A total of 101 patients completed the survey (response rate: 47%). Twelve survey participants completed interviews. In the survey, most patients identified changing family roles as important (76%), which was infrequently discussed with clinicians (31%). Most patients (86%) worried about the quality of their life in the future, and 74% said that not knowing what to expect in the future prevented them from making plans. The mean MUIS-A score was 85.5 (standard deviation 15.3). Interviews revealed three themes: (1) uncertainty of the future distresses participants; (2) participants want practical information from clinicians; and (3) communication preferences vary among participants. Participants experienced distressing uncertainty and wanted information about the future. Communication topics that were important to participants were not always addressed by physicians. Clinicians should address how chronic lung disease and lung transplant can directly impact patients' lives and support patients to cope with uncertainty.

Judge rules in favor of former employee

Case name: Buck‐Yael v. Washington University, No. 4:23CV492 (E.D. Mo. 03/28/24).

A Review of: “Saving Forest Ecosystems: A Century Plus of Research and Education at the University of Washington”

A Review of: “Saving Forest Ecosystems: A Century Plus of Research and Education at the University of Washington”

LMIC-06. WEB-BASED SURVEY RESULTS OF THE INTERNATIONAL PEDIATRIC NEURO-ONCOLOGY TUMOR BOARD AT WASHINGTON UNIVERSITY IN ST. LOUIS SCHOOL OF MEDICINE

Abstract BACKGROUND The International Pediatric Neuro-Oncology Tumor Board at Washington University in St. Louis School of Medicine (WUSM) was established in January 2021 as a monthly multi-disciplinary collaboration to help guide the care of pediatric central nervous system (CNS) tumor patients worldwide. The quarterly integration of Neurofibromatosis (NF) meetings expanded the initiative in September 2021. This survey explores participant experiences and their satisfaction aiming to optimize this international collaboration. METHODS A cross-sectional survey was distributed via a web-based platform in September 2023 amongst the participating healthcare professionals. RESULTS Fifty-three respondents from 23 countries completed the survey. The majority identified as pediatric hematology-oncologists (59%), and 10% as neuro-oncologists. Ninety-eight percent attended at least one session over two years, and 71% actively engaged in the quarterly NF meetings. Sixty percent attended more than five meetings, and 29% engaged in over 10 meetings. Barriers to attendance were primarily attributed to time constraints (71%) and conflicting professional or personal experiences (27%), while only 7% cited technical limitations and lack of awareness. Ninety-one percent reported that the meetings provide valuable educational insights and knowledge, particularly addressing challenging pediatric neuro-oncology cases. Additionally, 95% acknowledged the tumor board meetings’ positive contribution to professional development. Consensus recommendations emerging from the tumor board were reported to align with institutional recommendations (71%), be clear and comprehensible (93%,) and led to improved outcomes (93%). Notably, meeting frequency, leader expertise, knowledge enhancement, and level of engagement had positive influence on the participants’ willingness to attend the meeting. CONCLUSION Healthcare professionals attending the WUSM International Pediatric Neuro-Oncology Tumor Board reported the effectiveness of this virtual meeting format, its impact on professional development, and the alignment of recommendations with diverse institutional needs. The study provides valuable insights to further enhance the program’s sustainability, international collaboration, and overall effectiveness in improving global pediatric neuro-oncology patient care.

NFS-08. CLINICAL AND MOLECULAR FEATURES OF HIGH-GRADE GLIOMA IN CHILDREN AND ADULTS WITH NEUROFIBROMATOSIS TYPE 1: A PRELIMINARY ANALYSIS

Abstract BACKGROUND Individuals with neurofibromatosis type 1 (NF1) are at increased risk for developing high-grade glioma (HGG) relative to the general population. Despite the elevated incidence in NF1, adequately powered studies of HGG have not been performed to date, limiting understanding of the clinical course, prevalent treatment approaches, recurrent molecular features, and outcomes. METHODS Patients with NF1 and pathologic or molecularly confirmed high grade glioma and high-grade astrocytoma with piloid features at Children’s Hospital of Philadelphia, University of California San Francisco, Washington University, and Cincinnati Children’s Hospital Medical Center diagnosed between 2005 to 2021 were included. Retrospective clinical, molecular, treatment, and imaging data were collated and analyzed. RESULTS Thirty-four patients met eligibility criteria, 13 (38%) were female. The median age at diagnosis was 22.7 years; 10 were pediatric (children &amp;lt;18 years of age). The most common diagnoses included high-grade astrocytoma (7), anaplastic astrocytoma (8), glioblastoma multiforme (5), and high-grade astrocytoma with piloid features (5). Fifteen (44%) of tumors underwent biopsy only and 4 (12%) were gross totally resected. Nine tumors (26%) were considered to have transformed from a pre-existing low-grade lesion. In the 22 cases with molecular testing, the most prevalent genetic variants involved the NF1, CDKN2A/B, ATRX, TP53, and SUZ12 genes. Frontline treatment approach varied; however, 26 individuals (76%) received radiation as part of their initial therapy. Overall survival at 2 years was 52% (95% CI 33-67) across all ages and 70% (95% CI 33-89) in children. There was no significant difference in overall survival at 2 years by extent of tumor resection at diagnosis. CONCLUSIONS High grade glioma in individuals with NF1 demonstrate a high prevalence of alterations in the CDKN2A/B and ATRX genes, with a poor overall survival despite radiation-inclusive treatment regimens. Collection of additional patient data from collaborating institutions is ongoing to support further analyses.